Deprescribing antipsychotics in patients with Alzheimers disease and related dementias and behavioral disturbance in skilled nursing facilities

在熟练护理机构中取消阿尔茨海默病及相关痴呆症和行为障碍患者的抗精神病药物处方

• 批准号: 10634934
• 负责人: JOSHUA K LIN
• 金额: $ 89.29万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10634934
• 关键词: Acute; Address; Adopted; Adverse event; Affect; Algorithms; Alzheimer' s disease patient; Alzheimer' s disease related dementia; Antipsychotic Agents; Arrhythmia; Behavior; Behavior Therapy; Behavioral; Behavioral Symptoms; Certification; Cessation of life; Characteristics; Chronic; Clinical; Complex; Confusion; Data; Data Set; Delirium; Dementia; Detection; Dimensions; Dose; Dose Rate; Elderly; Electronic Health Record; Exclusion; Goals; Guidelines; Health; Heterogeneity; Hospitalization; Hypotension; Impaired cognition; Individual; Knowledge; Liver Dysfunction; Machine Learning; Measures; Medicare claim; Methods; Outcome; Pain management; Patient Selection; Patients; Pattern; Persons; Pharmaceutical Preparations; Pharmacological Treatment; Phenotype; Pneumonia; Polypharmacy; Predictive Value; Procedures; Process; Provider; Proxy; Randomized, Controlled Trials; Recommendation; Reporting; Research; Schedule; Scheme; Schizophrenia; Serious Adverse Event; Severities; Severity of illness; Signal Transduction; Skilled Nursing Facilities; Solid; Subgroup; Surveys; Symptoms; Time; United States Food and Drug Administration; Ventilatory Depression; Weight; adverse outcome; care delivery; clinical phenotype; comorbidity; comparative; comparative effectiveness analysis; comparative safety; data mining; electronic health database; electronic health information; evidence base; frailty; health assessment; high dimensionality; innovation; kidney dysfunction; medication safety; mortality; novel; participant retention; phenotyping algorithm; psychological symptom; psychotic; recruit; routine care; tool; treatment effect; trial comparing

Project Summary About 40-45% of people living with Alzheimer’s disease and related dementias (ADRD) reside in a skilled nursing facility (SNF). Behavioral and psychological symptoms of dementia (BPSD) occur in ~80% of older adults with ADRD living in an SNF. Antipsychotic medications (APMs) are the most commonly used pharmacological treatment for BPSD. Because APMs are associated with numerous adverse events, clinical guidelines recommend that their use should be limited to managing acute episodes and discontinued as soon as possible. However, studies have shown that APMs are often used in individuals with ADRD for sustained periods (≥6 months). Small randomized controlled trials (RCTs) comparing withdrawing vs. continuing APMs used for BPSD have yielded conflicting and confusing results that suggested deprescribing APMs had little or no benefits for adverse events. These RCTs were clearly underpowered, and they severely underrepresented frail and complex older adults with ADRD in routine care. There was also a lack of non-randomized studies addressing this critical knowledge gap because deprescribing APMs for behavior disturbance is highly informed by symptom severity, and confounding by disease severity can be very difficult to control unless detailed clinical information is available for research. Our objective is to assess the health effects of different APM deprescribing strategies for managing BPSD in an SNF. To provide solid evidence guiding the deprescribing process, we will assess the effects of discontinuing APMs with vs. without gradual dose reduction and different rates of dose tapering. We will integrate Medicare claims data with electronic health records (EHR), Minimum Data Set (MDS), and Certification and Survey Provider Enhanced Reporting (CASPER), covering >370,000 older adults with ADRD living in an SNF from 2013 to 2026. We will employ the clone-censor-weight approach, high-dimensional machine-learning-aided proxy adjustment methods, external adjustment, and instrumental variable analysis to minimize measured and unmeasured confounding. We will address three specific aims: 1) To evaluate the prescribing and discontinuation patterns and determine the barriers to APMs deprescribing among older adults with BPSD in an SNF. 2) To determine comparative health outcomes of different discontinuation strategies vs. continuation of APMs used for BPSD in older adults who reside in an SNF. 3) To determine the treatment effect heterogeneity by key clinical phenotypes when comparing continuation vs. different discontinuation strategies of APMs used for BPSD in older adults who reside in an SNF so that such deprescribing decisions can be tailored according to patient characteristics. The impact of this proposal is high because it will generate direct evidence to inform optimal management of psychotropic medications in older adults with ADRD living in an SNF. It will also yield a scalable analytical framework specializing in comparative safety and effectiveness analyses of deprescribing psychotropic treatments for behavioral and psychological symptoms of dementia.

项目概要 大约 40-45% 的阿尔茨海默病和相关痴呆症 (ADRD) 患者需要接受熟练的护理 大约 80% 的老年人会出现痴呆症的行为和心理症状 (BPSD)。 ADRD 生活在 SNF 中，抗精神病药物 (APM) 是最常用的药物。 由于 APM 与许多不良事件相关，因此临床指南。 建议其使用仅限于治疗急性发作并尽快停止使用。 然而，研究表明，APM 经常用于 ADRD 患者持续一段时间（≥6 月）的小型随机对照试验 (RCT)，比较用于 BPSD 的退出 APM 和持续 APM。 已经产生了相互矛盾和令人困惑的结果，表明取消 APM 对患者几乎没有好处或没有好处 这些随机对照试验显然动力不足，并且严重低估了脆弱和复杂的情况。 日常护理中患有 ADRD 的老年人也缺乏解决这一关键问题的非随机研究。 知识差距，因为针对行为障碍取消 APM 处方很大程度上取决于症状的严重程度， 除非有详细的临床信息，否则疾病严重程度的混杂可能很难控制 我们的研究目标是评估不同 APM 处方管理策略对健康的影响。 为了提供指导取消处方过程的确凿证据，我们将评估 SNF 中的 BPSD。 停用 APM 与不逐渐减少剂量以及不同的剂量逐渐减少率我们将进行整合。 医疗保险索赔数据包含电子健康记录 (EHR)、最低数据集 (MDS) 以及认证和 调查提供者增强报告 (CASPER)，覆盖居住在 SNF 的超过 370,000 名患有 ADRD 的老年人 从2013年到2026年。我们将采用克隆审查权重方法，高维机器学习辅助 代理调整方法、外部调整和工具变量分析，以尽量减少测量和 我们将解决三个具体目标：1）评估处方和 停药模式并确定在患有 BPSD 的老年人中停用 APM 的障碍 SNF。2) 确定不同停药策略与继续治疗的比较健康结果 APM 用于居住在 SNF 的老年人的 BPSD 3) 确定治疗效果的异质性。 比较所用 APM 的继续治疗与不同停药策略时的关键临床表型 针对居住在 SNF 的老年人的 BPSD，以便可以根据以下情况制定此类取消处方的决定： 该提案的影响很大，因为它将产生直接的证据来提供信息。 对生活在 SNF 中的患有 ADRD 的老年人进行精神药物的优化管理也将产生以下效果。 可扩展的分析框架，专门从事停用药物的比较安全性和有效性分析 针对痴呆症行为和心理症状的精神药物治疗。